Nearly two-thirds of the adult population of the United States is overweight or obese. One of the serious consequences of this obesity epidemic is the growing evidence that obesity increases risk for several common cancers. Hyperinsulinemia, and altered levels of adipocyte hormones, insulin-like growth factors and markers of inflammation often accompany obesity and may provide the mechanistic explanation for these observed associations of obesity with cancer. IGF-1 inhibits apoptosis and stimulates proliferation and both insulin leptin are mitogenic. On the other hand, obesity inhibits adiponectin, which has been associated with both the inflammatory response and carcinogenesis. Dietary patterns are related to the synthesis, metabolism and distribution of these biomarkers. For example, diets can be characterized relative to their influence on the postprandial glucose response;e.g., diets rich in simple sugars and refined carbohydrates have a high glycemic index because they produce a rapid rise in blood glucose. Foods such as meats, legumes, and high-fiber fruits and vegetables produce a low rise in blood glucose and have a low glycemic index. Despite the plethora of scientific papers suggesting that high-glycemic-index foods increase cancer risk, very few intervention studies in humans have evaluated the action of low and high glycemic foods on biomarkers of cancer risk. We propose a randomized, controlled cross-over feeding trial in 88 lean (BMI<25) and obese men and women (BMI>30). Participants will be randomized to consume either a low- or highglycemic- load diet for four weeks, followed by a four week wash-out period, then cross-over to the other arm. Blood samples will be collected at the beginning and end of each diet period and assayed for insulin, glucose, IGF-1, IGFBP3, leptin, adiponectin, C-reactive protein, serum amyloid A, and interleukin-6. This study will provide a rigorous test of common dietary patterns in humans that will allow us to directly test dietrelated mechanisms of obesity and biomarkers of carcinogenesis. Importantly, by recruiting both lean and obese persons, we will be able to examine whether there is a differential response to the high- and lowglycemic load diets for lean vs. obese individuals. This study will provide data of immediate clinical and public-health benefit.